Neoadjuvant therapy using LHRH analogues or anti-androgenic treatment before surgery to decrease the prostate and tumour size and lower PSA levels is being investigated to assess its effect on survival and recurrence. Patients are followed up with assessment of PSA serum levels as PSA should become undetectable in the blood within 2 days after surgery.
Patient follow up is then performed by re-assessing the pathology reports and performing bone scintography to assess for distant metastasis.
The faster the PSA doubling time, the greater the risk for clinical relapse, which is defined by signs and symptoms of recurring cancer. As there are few recurrences after 7 years, this approximates the percent of patients that will remain disease free. Radiation therapy is the other modality commonly used for curative treatment of low risk, localized prostate cancer. There have been very few reliable randomized controlled trials comparing radical prostatectomy and radiation therapy for low risk disease.
The outcome of radiation therapy is assessed by PSA levels. Unlike radical prostatectomy, it may take years before PSA reaches nadir, the lowest post-treatment level.
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The nadir level varies between individuals and depends on pre treatment PSA levels. Brachytherapy can also be used to treat prostate cancer alone or in combination with external beam radiotherapy. These seeds remain in the prostate gland and kill rapidly dividing tumour cells. The procedure involves minimal discomfort and is done under anaesthetic. Patients are discharged without a catheter the same day. No randomized controlled studies have compared this to conventional external beam radiotherapy, but retrospective studies have shown similar efficacies to both external beam radiotherapy and radical prostatectomy.
Patients may decide to wait before undergoing radical prostatectomy or radiotherapy. This option is offered according to the Epstein criteria or a life expectancy of less than 10 years. In the US, one in four men is managed expectantly. Watchful waiting is used when treatment is not expected to alter life expectancy, or the patient does not want to pursue treatment.
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Palliative treatment is given when the patient becomes asymptomatic. Active surveillance involves closer observation and treatment options used when the disease progresses with intention to cure. In the watchful waiting approach, patients are monitored by following PSA levels and performing DRE examination once or twice yearly. Once patients are symptomatic, palliative treatment is provided. Results were most significant for men less than 65 years. With active surveillance, another biopsy may be performed 3 months after initial assessment to reassess cancer extent.
Another biopsy is done 3 years after initial treatment. Follow up is done by urologists or radiation oncologists depending on the future treatment option surgery or radiotherapy that is chosen. Progression to stage T3, Gleason grades of on re-biopsy, PSA doubling time faster than 3 years based on 3 lab results and patient choice are all indications for beginning treatment. Curative treatment such as radiotherapy and radical prostatectomy are then used. Low risk prostate cancer is treated curatively by radical prostatectomy and radiotherapy. Expectant management may also be employed where patients are monitored and treatment is initially withheld until the disease progresses.
The efficacy of neoadjuvant and adjuvant hormonal therapy in low risk prostate cancer is being investigated. The best treatment for this stage of cancer is not clear as there has not been any long term randomized controlled trials showing clear evidence. Numerous modalities may be employed including: intermittent and continuous hormonal treatment, radical prostatectomy with or without hormones, radiotherapy with or without hormones, and expectant management.
Randomized controlled trials have shown a clear benefit with increased survival with the addition of hormonal therapy to radiotherapy for higher risk disease.
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Surgery alone for intermediate risk cancer may be associated with morbidity and mortality with eventual dissemination. Androgens control the proliferation of prostate gland cells by three mechanisms: increasing DNA synthesis and proliferation, preventing apoptosis, and preventing the limitation of the number of cells in the gland.
Hormonal therapy can be used for prostate cancer treatment in three ways. It can be used as neoadjuvant therapy, which is therapy provided before radiation or prostatectomy. Therapy can also be provided as an adjuvant, which is given during or after radiation or surgery. It can also be the primary therapy, which is first line treatment for advanced metastatic cancer.
They may be given for months prior to radiation and continued for a total duration of years.
Treatment is provided by giving anti-androgens and LHRH analogues. When LHRH agonists are first given there is a surge in testosterone. The anti-androgen medications block the androgen receptor on prostate cells competitively and thus prevent binding of the testosterone to the prostate cells during the surge. Once the LHRH agonist has been present for several weeks, the surge settles and the anti-androgens can be stopped. Watchful waiting is considered if life expectancy is less than 10 years depending on patient preference.
Active surveillance may also be done regardless of life expectancy. Prostate cancer is classified as low, intermediate and high risk in Canada and this system is used for treatment selection. Intermediate risk prostate cancer can be treated using numerous modalities including prostatectomy and radiotherapy with and without hormonal therapy or hormone therapy alone.
Patients may also choose expectant management. If metastasis are not present, radiotherapy or androgen ablation are used alone or combined. Surgery is generally not an option at this stage. If metastases are present, first line therapy is androgen ablation. If there are no metastasis present, radiotherapy is often combined with neoadjuvant hormonal therapy and adjuvant hormone therapy. The combination of external beam radiotherapy and hormones improves survival in locally advanced disease. The total duration of hormones is usually years.
High risk prostate cancer may be treated with radiotherapy, hormones alone or together, but radical prostatectomy is generally not an option. This may cause an increase in symptoms such as bone pain, obstruction, or rarely, spinal cord compression. It is recommended to use an anti-androgen for 4 weeks to prevent this flare-up.
By three weeks, the analogues will cause a suppression of gonadotropin release leading to a drop in testosterone levels. Patients are kept on a constant dose. PSA levels are monitored to assess for prostate gland suppression. There are numerous side effects to treatment which are listed below. With continuous treatment, all the malignant cells may not be killed and the presence of anti-androgens may select for androgen-insensitive cells.
This may cause a quicker progression to an androgen-independent state where malignant prostate cells can divide and replicate even in the absence of androgens. Intermittent hormonal treatment can be used to prevent some of the side effects from anti-androgen therapy and may have a role in decreasing progression to androgen-independence. If PSA levels are stable at weeks after treatment began, therapy can be interrupted at 36 weeks.
Therapy is resumed when the PSA levels return to pre-treatment levels.
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Studies comparing continuous and intermittent therapy have shown varying effects on survival. It is theorized that the prostate may depend on the adrenal androgen production and this may cause cancer recurrence. Removal of the testes is done as a day surgery under local or general anaesthetic. There is little associated morbidity but majority of patients prefer hormonal therapy when given the option. This is not commonly used now.
If the treatment plan is palliative, patients may choose radiotherapy and hormones alone or combined or may also elect to undergo hormonal therapy and TURP as needed for symptomatic relief. Most bone metastases are osteoblastic but some may contain osteolytic lesions. Alkaline phosphate serum levels are often elevated and can be followed along with bone scans and plain films. Pathological fractures and bone pain may also occur. Treatment may include analgesics, hormonal therapy, radiotherapy and chemotherapy for pain relief.
Another option is treating with biphosphonates to decrease skeletal complications such as fractures, osteopenia or the need for surgery, chemotherapy or radiation. According to the BC Cancer Agency, biphosphonates do not affect survival rates, pain, or quality of life. The first line treatment for metastatic prostate cancer is androgen ablation by hormonal therapy or bilateral orchidectomy. Palliative treatment may include a variety of modalities for symptomatic relief depending on location of metastasis. Molecular factors such as gene mutations also affect prognosis. A PSA relapse after treatment is defined differently depending on the treatment modality.
After prostatectomy, a PSA value above 0. After radiation therapy, an increase in PSA value after reaching the lowest level which may take years may be considered as a PSA relapse. Biochemical evidence of no disease BNED depends on spread beyond the capsule, positive margins, seminal vesicle involvement, and nodal disease. PSA biochemical failures are times more common than clinical failures which are defined by signs and symptoms of recurrent cancer. Local failures are greater if there are positive margins after surgery.
Redevelopment of nodules on DRE may also indicate relapsing and will require additional treatment. Prostate cancer biochemical relapse can be assessed by monitoring PSA levels.